Acquired immune deficiency syndrome (AIDS) has rapidly become one of the major causes of death in the world. It is estimated that over 40 million people are infected with the human immunodeficiency virus (HIV), which is the causative agent of AIDS. In 1985, 3′-azido-3′-deoxythymidine (AZT) was approved as the first synthetic nucleoside to inhibit the replication of HIV. Since then, a number of other synthetic nucleoside analogs have been proven to be effective against HIV. After cellular phosphorylation to the triphosphate form by cellular kinases, the nucleotides are incorporated into a growing strand of viral DNA and cause chain termination due to the absence of the 3′-hydroxyl group.
Carbocyclic nucleosides are structural analogs to nucleosides in which the furanose oxygen is replaced by a methylene group. Similar to native nucleosides, carbocyclic nucleosides can behave as inhibitors of the enzymes. However, because carbocyclic nucleosides lack the labile glycosidic linkage between heterocycle and sugar of native nucleosides, they are not susceptible to hydrolysis by phosphorylases or phosphotransferases.
Carbocyclic nucleosides have been the subject of extensive investigation because of the variety of biological properties displayed by these compounds. Of particular interest is the potential of carbocyclic nucleosides for use in antiviral, antitumor and anticancer chemotherapeutic applications. Perhaps the best known examples of such carbocyclic nucleosides are Abacavir and Carbovir, both of which show great promise as anti-HIV agents.
Carbovir has been reported as the first carbocylic nucleoside analogue, with potent anti-HIV activity in vitro; its discovery provided a base for the synthesis of other carbocyclic analogues. The first synthesis of Carbovir has been accomplished in 1990 by Vince et al., as a racemic mixture of two enantiomers. Afterwards, a chemoenzymatic synthesis of both enantiomers of Carbovir, has been reported. The natural (−)-enantiomer of Carbovir is primarily responsible for the antiviral activity.
Chemically Carbovir is represented as 2-Amino-9-[(1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-yl]-1,9-dihydro-6H-purin-6-one and structurally as shown below:

Abacavir sulphate, having the brand name ZIAGEN®, is a synthetic carbocyclic nucleoside analogue with inhibitory activity against HIV-1. The chemical name of Abacavir sulfate is (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. It has a molecular formula of (C14H18N6O)2.H2SO4 and a molecular weight of 670.76 daltons. It has the following structural formula:

U.S. Pat. No. 5,034,394 discloses a process for the preparation of (1S,4R)-4-amino-2-cyclopentene-1-methanol dibenzoyl-D-tartrate which comprises reaction of racemic 2-azabicyclo[2.2.1]hept-5-en-3-one with hydrogenchloride in methanol to give (±)cis-methyl-4-amino-2-cyclopentene-1-carboxylate hydrochloride which on reduction with DIBAL-H in hexane gave racemic 4-amino-2-cyclopentene-1-methanol which is further subjected to resolution with dibenzoyl-D-tartaric acid to give (1S,4R)-4-amino-2-cyclopentene-1-methanol dibenzoyl-D-tartrate. The process is shown in the scheme given below:

U.S. Pat. No. 6,448,402 discloses a process for the preparation of compound of (1S,4R)-4-amino-2-cyclopentene-1-methanol D-hydrogen tartrate which comprises resolution of racemic 1-amino-4-(hydroxymethyl)-2-cyclopentene with D(−)-tartaric acid in methanol at reflux temperature followed by cooling to 20° C. for about 2 hours gave crystals of compound of (1S,4R)-4-amino-2-cyclopentene-1-methanol D-hydrogen tartrate, Racemic 1-amino 1 (hydroxymethyl)-2-cyclopentene is prepared in turn by reduction of 2-azabicyclo[2.2.1]hept-5-en-3-one using lithium borohydride. The process is shown in the scheme given below:

U.S. Pat. No. 6,495,711 discloses a process for the preparation of compound of (1S,4R)-4-amino-2-cyclopentene-1-methanol L-hydrogen tartrate which comprises resolution of racemic reacting racemic 2-azabicyclo[2.2.1]hept-5-en-3-one with methanol in the presence of HCl gas followed by resolution of the obtained compound with L(+)-tartaric acid in water, addition of triethylamine and then workup resulted in crystals of (1S,4R)-methyl-4-amino-2-cyclopentene carboxylate L-hydrogen tartrate. The process is shown in the scheme given below:

Nucleosides, Nucleotides & Nucleic acid, 19(1&2), 297-327, 2000 discloses a process for the preparation of (1S,4R)-4-amino-2-cyclopentene-1-methanoldibenzoyl-D-tartrate which comprises reduction of tosylate salt of 4-amino-2-cyclopentene-1-carboxylate using lithium aluminium hydride in THF to give racemic 4-amino-2-cyclopentene-1-methanol followed by resolution of the same with dibenzoyl-D-tartaric acid in ethanol and acetonitrile to give (1S,4R)-4-amino-2-cyclopentene-1-methanol dibenzoyl-D-tartrate. The process is shown in the scheme given below:

The methods for preparing compound of (1S,4R)-4-amino-2-cyclopentene-1-methanol or its salts shown in the above prior art are disadvantageous in that they employ expensive, toxic reagents and require extreme reaction conditions, multiple steps thereby rendering them unsuitable for bulk production.
Accordingly, there has been a need to develop a simple and industrially viable process for preparing (1S,4R)-4-amino-2-cyclopentene-1-methanol or its salt of compound of Formula III by using intermediate of Formula IV.